Antibiotic breakthrough may signal the end of drug-resistant superbugs

Scientists have come across a potential game-changer in the fight against drug-resistant superbugs - a new class of antibiotic
that is resistant to resistance. Not only does the new compound - which comes from soil bacteria - kill deadly superbugs like MRSA, but
also - because of the way it destroys their cell wall - the pathogens will find it very difficult to mutate into resistant
strains.

Scientists have discovered a new compound in soil bacteria that kills MRSA and also appears to prevent it from evolving into other drug-resistant forms.

Kim Lewis, a microbiologist and professor at Northeastern University in Boston, MA, and colleagues report their discovery in the
journal Nature.

Many of the antibiotics in use today were discovered decades ago, and since then, microbes have evolved into resistant strains that
do not succumb to them.

For instance, according to the World Health Organization (WHO), in 2012, there were about 450,000 new cases of multidrug-resistant
tuberculosis (MDR-TB) worldwide. And extensively drug-resistant tuberculosis (XDR-TB) has been identified in 92 countries.

Bacteria that cause common infections such as urinary tract infections, pneumonia, bloodstream infections, are also becoming
increasingly resistant and hard to treat. For instance, a high percentage of hospital-acquired infections are caused by a highly
resistant form of Staph - methicillin-resistant Staphylococcus aureus or MRSA.

This alarming scenario - coupled with the fact there are hardly any new antibiotics in the pipeline - led the WHO recently to warn
we are approaching a "post-antibiotic era" where people could die from ordinary infections and minor injuries.

Most antibiotics in use come from soil microbes

Most of the antibiotics used in human and animal medicine today come from soil microbes - for millions of years they have been
producing toxic compounds to fight off other enemy microbes. For example penicillin, the first successful antibiotic, comes from the
soil fungus Penicillium.

But there is a major problem with researching soil microbes - they are very difficult to culture in the lab. This means that as many
as 99% of the microbes on our planet remain under-researched as sources of new antibiotics because they refuse to grow in lab cultures.
That is until now.

Prof. Lewis and colleagues developed a way to culture bacteria in their natural environment. This uses a device that they call a
"diffusion chamber" where the soil microbes they want to grow are separated into individual chambers sandwiched between two semi-permeable membranes. They then bury the device back in the soil.

Thus, through the semi-permeable membranes, the bacteria become exposed to the highly complex mix of other microbes and compounds of
the soil, and grow readily as if they were in the soil. This way, the researchers produced bacterial colonies large enough to research
back in the lab.

10,000 colonies yielded 25 potential new antibiotics, including one superbug-buster

By repeatedly using the diffusion chamber to culture different species of soil bacteria, the team tested about 10,000 bacterial
colonies to see if any produced compounds that could stop the growth of S. aureus.

They found 25 potential antibiotics, of which one, teixobactin, appeared the most powerful.

In the lab, teixobactin, killed a broad range of pathogenic bacteria, including the drug-resistant superbugs MRSA and VRE
(vancomycin resistant enterococci).

Further tests in mice showed promising results against bacteria that cause septicemia, skin and lung infections.

Teixobactin breaks down the bacterial cell wall - the pathogen's key defence against attack. The researchers believe this means the
microbe can mutate all it likes, but its cell walls will always be its Achilles heel.

Prof. Lewis says, "Teixobactin's dual mode of action and binding to non-peptidic
regions suggest that resistance will be very difficult to develop."

He and his colleagues found that repeated exposure to the drug did not produce any resistant mutations in Staphylococcus
aureus or Mycobacterium tuberculosis, the bacterium that causes most cases of TB.

They conclude: "The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development
of resistance."

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